The overall objectives of this program project research grant are the elucidation of the pathophysiologic characteristics of cystic fibrosis and the evaluation and development of therapeutic measures. The grant is administered and funded by two institutes, NIAMDD and NHLBI. This progress report covers that portion of the program which is under the jurisdiction of NIAMDD and which consists of one core facility and three research projects. A clinical research project is investigating the hyperglycemia of CF by determining the levels and interrelations of hormones regulating blood glucose in patients as they progress from normal glucose tolerance to severe intolerance and by evaluating the pathophysiologic effects of hyperglycemia. These investigators have found that many cystic fibrosis patients do not have normal glucose tolerance even though they do not demonstrate frank or symptomatic hyperglycemia. Two research projects are investigating epithelial water and electrolyte transport with the long term objective of understanding the pathophysiology of the exocrine electrolyte abnormalities of CF. One of these projects using rat parotid retrograde perfusion assay, has found that polyamine-derived polycations isolated from CF seminal plasma inhibit sodium transport. Polycations with similar properties have been isolated from CF saliva. This project has had a change of emphasis toward polyamine catabolism in human exocrine glands. The second basic research project is investigating cellular mechanisms of epithelial electrolyte transport and has demonstrated that sodium transport inhibitors from CF saliva will inhibit short-circuit current in the rat colon. Contrary to reports from another laboratory (Araki, et al., Pediat. Res., 9:932, (1975), CF serum does not inhibit glucose transport in the rat small intestine.